Haplotype analyses with the human leucocyte antigen and tumour necrosis factor‐alpha genes in narcolepsy families

Abstract
Our previous study suggested that the tumour necrosis factor‐alpha gene with thymine residue at position –857 in its promoter region [TNF‐α(–857T)] could be associated with human narcolepsy independently of a strong association of the human leucocyte antigen (HLA)‐DRB1*1501 with the disorder. To understand the relationship of DRB1*1501 with TNF‐α(–857T) in narcoleptic patients, we investigated 28 members of four Japanese narcolepsy families and determined the haplotypes with the HLA‐B, TNF‐α(–857C/T) and HLA‐DRB1 in the members. The resultant haplotypes indicated that not only the DRB1*1501‐TNF‐α(–857C) haplotype but also the DRB1*1501‐TNF‐α(–857T) haplotype, which is rare in healthy individuals and may have a strong predisposition to the disorder, were present in the affected members. From the chromosomal recombination observed in a few members, it is possible that chromosomal recombination could play a role in the generation of the rare DRB1*1501‐TNF‐α(–857T) haplotype.